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Errors with Half Life Determination

Calculating elimination rate constants and half lives can be challenging in patients that are unstable. For drugs that are eliminated renally, it is important to ensure that renal function is stable when accessing creatinine clearance values. Using two post distribution serum drug levels without a dose administered in between may not provide the most accurate assessment of the patient’s renal function. Using this approach may lead to errors in half life calculations that result in over estimating renal function.

When serum creatinine values are trending up, this suggests that creatinine clearance is decreasing and renal function is declining. If therapeutic options are limited and drug treatment is to be continued, then adjustments in dosing will be required. We equate this to “trying to hit the moving target.” This typically requires extending the dosing interval in anticipation of a longer half life. For instance, if using a q8 dosing interval, it may be necessary to extend to q16 or beyond.

When serum creatinine values are trending down, this suggests that creatinine clearance is improving with improving renal function. Here, it may be necessary to reduce the dosing interval. This may occur when resistance is a concern and we need to maintain adequate serum concentrations above the MIC. However, we must proceed with due caution in meds that are nephrotoxic eg. aminoglycosides.

Repeated drug levels may be necessary if therapy is to be continued for more than 2-3 days to ensure levels remain therapeutic.

 

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